可溶性c-Met对鼻咽癌细胞的增殖影响探讨

Effect of sMet on the proliferation of nasopharyngeal carcinoma cell line CNE-2Z

目的探讨肝细胞生长因子受体(c-Met)可溶性形式(soluble c-Met,sMet)对低分化鼻咽癌上皮细胞系CNE-2Z的生物学效应。方法HGF、sMet等分别处理培养的人鼻咽癌CNE-2Z细胞,采用MTT比色法观察各组处理24、48和72 h后对鼻咽癌CNE-2Z细胞增殖的影响;Western Blot检测以上各组的Akt信号的磷酸化水平的改变。结果HGF组一直都维持对CNE-2Z细胞较高的促增殖效应,而在sMet竞争结合HGF后,促增殖效应明显受抑;加入LY294002(Akt信号通路的抑制剂)对HGF促增殖能力具有同样的抑制效果。HGF能激活Akt信号通路,促使Akt信号分子的磷酸化,sMet竞争结合HGF后,Akt的磷酸化水平与HGF组相比显著下降。结论在体外培养的人鼻咽癌CNE-2Z细胞模型中,证实sMet可以阻断HGF对鼻咽癌CNE-2Z细胞增殖的促进作用,其可能机制与AKT信号通路有关。

Objective To examine the effect and mechanism of the soluble c-Met （sMet） form of hepatocyte growth factor re-ceptor,on nasopharyngeal carcinoma cell line CNE-2Z. Methods The cell proliferation ability was detected by MTT,treated with HGF,sMet and so on. Western blotting was applied to detect the expression of phospho-Akt. Data were analyzed with SPSS soft-ware. Results HGF has been shown to stimulate CNE-2Z cell growth in cell line model,the effect of inhibition by sMet on the growth potential of NPC cell lines. Western blotting to show the blocking effect of sMet on HGF-induced activation of AKT ,and Down-regulation of phospho-Akt was detected in CNE-2Z cells after LY294002 （the inhibitor of Akt）treatment. Conclusion sMet inhibition resulted in suppression of CNE-2Z cell growth potential via down-regulation of phospho-Akt signaling pathway. HGF-sMet is an important therapeutic target for NPC that warrants further studies and clinical trials.